Model-based reconstructions for intravoxel incoherent motion and diffusion-tensor imaging parameter map estimations

PURPOSE: Intravoxel incoherent motion (IVIM) imaging and diffusion-tensor imaging (DTI) facilitate non-invasive quantification of tissue perfusion and diffusion. Both are promising biomarkers in various diseases and a combined acquisition is therefore desirable. This comes with challenges, including noisy parameter maps and long scan times, especially for the perfusion fraction f and pseudo-diffusion coefficient D*. A model-based reconstruction has the potential to overcome these challenges. As a first step, our goal was to develop a model-based reconstruction framework for IVIM and combined IVIM-DTI parameter estimation. METHODS: The IVIM and IVIM-DTI models were implemented in the PyQMRI model-based reconstruction framework and validated with simulations and in vivo data. Commonly used voxel-wise nonlinear least-squares fitting was used as reference. Simulations with the IVIM and IVIM-DTI models were performed with 100 noise realizations to assess accuracy and precision. Diffusion-weighted data were acquired for IVIM-reconstruction in the liver (n=5) as well as for IVIM-DTI in the kidneys (n=5) and lower-leg muscles (n=6) of healthy volunteers. The median and interquartile range (IQR) values of the IVIM and IVIM-DTI parameters were compared to assess bias and precision. RESULTS: With model-based reconstruction, the parameter maps exhibit less noise, which was most pronounced in the f and D* maps both in the simulations and in vivo. The bias values in the simulations were comparable between model-based reconstruction and the reference method. The IQR was lower with model-based reconstruction compared to the reference for all parameters. CONCLUSION: Model-based reconstruction is feasible for IVIM and IVIM-DTI and improves the precision of the parameter estimates, particularly for f and D* maps

Anoctamin-4 is a bona fide Ca2+-dependent non-selective cation channel

Abstract Changes in cell function occur by specific patterns of intracellular Ca2+, activating Ca2+-sensitive proteins. The anoctamin (TMEM16) protein family has Ca2+-dependent ion channel activity, which provides transmembrane ion transport, and/or Ca2+-dependent phosphatidyl-scramblase activity. Using amino acid sequence analysis combined with measurements of ion channel function, we clarified the so far unknown Ano4 function as Ca2+-dependent, non-selective monovalent cation channel; heterologous Ano4 expression in HEK293 cells elicits Ca2+ activated conductance with weak selectivity of K+ > Na+ > Li+. Endogenously expressed Ca2+-dependent cation channels in the retinal pigment epithelium were identified as Ano4 by KO mouse-derived primary RPE cells and siRNA against Ano4. Exchanging a negatively charged amino acid in the putative pore region (AA702–855) into a positive one (E775K) turns Ano4-elicited currents into Cl− currents evidencing its importance for ion selectivity. The molecular identification of Ano4 as a Ca2+-activated cation channel advances the understanding of its role in Ca2+ signaling

Regulated on Activation, Normal T cell Expressed and Secreted (RANTES) drives the resolution of allergic asthma

Abstract RANTES is implicated in allergic asthma and in T cell-dependent clearance of infection. RANTES receptor family comprises CCR1, CCR3, and CCR5, which are G-protein-coupled receptors consisting of seven transmembrane helices. Infections with respiratory viruses like Rhinovirus cause induction of RANTES production by epithelial cells. Here, we studied the role of RANTES in the peripheral blood mononuclear cells in cohorts of children with and without asthma and validated and extended this study to the airways of adults with and without asthma. We further translated these studies to a murine model of asthma induced by house dust mite allergen in wild-type RANTES and CCR5-deficient mice. Here we show an unpredicted therapeutic role of RANTES in the resolution of allergen-induced asthma by orchestrating the transition of effector GATA-3+CD4+ T cells into immune-regulatory-type T cells and inflammatory eosinophils into resident eosinophils as well as increased IL-10 production in the lung